Treatment patterns and outcomes among patients with EGFR-mutant advanced NSCLC in the frontline and post-osimertinib settings

Osimertinib is recommended frontline therapy for patients with EGFR-positive advanced non-small cell lung cancer (NSCLC). This study characterizes real-world treatment patterns and outcomes in frontline and post-osimertinib settings.

Data from the ConcertAI Patient360 NSCLC database (electronic medical records from >100 US oncology practices) were curated by nurse practitioners to determine date of metastatic diagnosis, tumor progression, treatment patterns, survival outcomes, etc. Included patients (≥18 y) had confirmed diagnosis of advanced/metastatic NSCLC ≤30 days after frontline therapy initiation and genetic testing confirming common EGFR mutation (exon 19 deletions, L858R); patients on osimertinib began treatment 8/2015‒7/2020. Treatment patterns and outcomes in the advanced/metastatic disease setting were assessed in three cohorts: 1) patients receiving any frontline therapy regardless of osimertinib use (assessed from start of frontline therapy for advanced disease); 2) patients whose disease progressed on osimertinib monotherapy and who started a subsequent line of therapy (LOT) (assessed from start of LOT following osimertinib); and 3) patients whose disease progressed after osimertinib, progressed after platinum chemotherapy, and who started a subsequent LOT (assessed from start of LOT following the platinum-containing therapy that immediately followed osimertinib).

In cohort 1, frontline therapy (n=979) comprised osimertinib alone or in combination in 40% of patients and other tyrosine kinase inhibitor (TKI) regimens in 52%. In cohort 2 (n=167), 44% received platinum-chemotherapy and 20% osimertinib retreatment as combination therapy. In cohort 3 (n=38), 47% went on to receive non-platinum-based chemotherapy or immuno-oncology monotherapy, and 32% were re-exposed to osimertinib, either as monotherapy (5%) or in combination therapy (26%). Outcomes are shown in the Table. Patients in cohort 2 were further examined by LOT in which osimertinib was used. For those who progressed on frontline osimertinib (n=53), median progression free survival (mPFS) and overall survival (mOS) were 4.3 and 10.4 months from the start of post-osimertinib LOT; 55% received a platinum-based combination in the LOT following osimertinib progression. For cohort 2 patients who progressed on 2nd- or later-line osimertinib (n=114), mPFS and mOS were 3.2 and 10.1 months from the start of post-osimertinib LOT; 28% of patients received TKI combination therapy and 39% received a platinum-based combination in the LOT following osimertinib progression.

A variety of treatments are used after osimertinib including osimertinib retreatment; outcomes demonstrate reduced duration of treatment and survival after each additional LOT, correlated with disease progression. There is an urgent need for newer, more effective therapeutics after osimertinib treatment.